TW200808295A - Use of agomelatine in obtaining medicaments intended for the treatment of generalized anxiety disorder - Google Patents

Abstract

The present invention relates to the use of agomelatine, or N-[2-(7-methoxy-1-naphthyl) ethyl] acetamide, in obtaining medicaments intended for the treatment of Generalized Anxiety Disorder.

Description

200808295 IX. INSTRUCTIONS OF THE INVENTION: TECHNICAL FIELD OF THE INVENTION The present invention relates to agomelazole or hydrazone-[2-(7-methoxy-indolyl)ethyl]acetamide of formula (1):

And the use of hydrates, crystalline forms thereof, and pharmaceutically acceptable acids or test addition salts for the manufacture of a medicament for the treatment of generalized anxiety disorder or gAD. [Prior Art] Agomelatine or lip [2-(7-methoxy-1-naphthyl)ethyl]acetamide has a dual desire to act on the one hand for the melatonin receptor system The agent, on the other hand, is an antagonist of the 5-HT2C receptor. These properties make it in the central nervous system and more particularly in the treatment of major depression, seasonal affective disorder, sleep disorders, cardiovascular pathology, digestive system pathology, insomnia and fatigue due to jet lag, appetite disorders and obesity Active in it. Agometaine, its preparation and its use in therapy are disclosed in European Patent Specification EP 0 447 285 and EP 1 564 202. Applicants have now discovered agomelatine or [2-(7-methoxy-1-naphthyl)ethyl]acetamide and its hydrates, crystalline forms and pharmaceutically acceptable acids or The addition salts have been shown to have important properties for the treatment of generalized anxiety disorder. The characteristics of generalized anxiety disorder are quite numerous and unreasonable anxiety, and its non-119756.doc 200808295 often meets well-defined criteria and constitutes a complete morbid nature (300.02-DSM IV-Mental Troubles Diagnostic and Statistic handbook, 4th edition) , American Psychiatric Association) This chronic pathology society causes many related annoyances and (especially) cognitive dysfunction, more specifically, thought and intellectual performance, changes in reasoning, judgment, and therefore implementation, but it also leads to clumsiness, A source of psychomotor disease that has a reduced ability to respond or is even incapable of responding (Wittchen HU et al., Arch Gen Psychiatry, 1994, 51(5), 355-364)

The specificity of the condition is additionally recognized by the US and European health agencies having published guidelines for the development of specific drugs that meet this need (Committee for Proprietary Medicinal Products (CPMP)/EWP/4284/02/ London-2005 1 -Guideline on the clinical investigation for the treatment of medicinal products indicated for Generalized Anxiety Disorder) o The latest epidemiological studies show that for this pathology, 5% to 6% of the world's population and up to 10% of 40 years old The incidence of women above. Therefore, the impact of this pathological condition is important from a health and economic standpoint. There is currently no fully satisfactory approved treatment for generalized anxiety disorder. Benzodiazepines have long been the primary treatment and are still used in some countries. Recently, molecules such as venlafaxine, paroxetine or escitalopram have been recommended. However, their different treatments have many side effects, the most frequently reported side effects being sedation, drug dependence, alcohol allergy, and cardiovascular and/or gender side. In addition, in most cases, treatment will stop. Stopping the syndrome (disc〇ntinuati〇n face can not be ignored. Another cause unacceptable syndrome). Research on the novelty of this pathology So, as highlighted in the CPMP guidelines, treatment is necessary. Agomelatine, a novel chemical nature with innovative pharmacological properties, has been shown to be highly potent in the relative placebo-controlled clinical studies in the case of Yan 4 depression. The agomela has been found to be due to its pharmacological properties. Can be used for generalized anxiety disorder. A clinical study comparing placebo in patients with generalized anxiety disorder shows that agomelatine is indeed suitable for the treatment of this condition. In addition to the effects observed in the treatment of generalized anxiety and illness, Agora's Ding also has a good acceptability profile for patients: in particular, Agomera: no usual associated with psychotropic drugs Side effects. In their role, Tian Tian 4 observed that the drug was stopped when he was treated with a typical Jingshen treatment. • Jun sheep was not observed with agomelatine, and agomelatine became this pathology. The choice of treatment. SUMMARY OF THE INVENTION The present invention relates to the preparation of a drug for the treatment of generalized anxiety disorder in the form of agomelatine and its hydrate, crystal form (adhesive and pharmaceutically acceptable + (4) test addition salts. Use of the composition. The present invention relates to the use of agomelatine obtained in the form of ° 1 described in the patent specification EP 1 564 202 for the preparation of a pharmaceutical composition for the treatment of generalized anxiety disorder. 119756.doc 200808295 The pharmaceutical compositions may be suitable for burial, % by oral, parenteral, transdermal, I-rectal or trans-oral routes and in particular in the form of L ° Keyring agent, sublingual lozenge, pill, gelatin capsule, gelatinous preparation, suppository 'cream, ointment, epidermal gel, etc. Except for agomelatine and depending on the situation, the emotional stability (4), according to this The pharmaceutical composition as set forth comprises one or more excipients selected from the following

Or carrier: diluent, lubricant, binder, disintegrant, adsorbent, coloring agent, sweetener, etc. By way of non-limiting example, it may be mentioned: ♦ trans-released lactose, lactose, dextrose, sucrose, mannitol, sorbitol cellulose, glycerol, ♦ 霹 / spear 漱 二 二, talcum powder, hard Fatty acid and its magnesium and calcium salts, polyethylene glycol, ♦ Christine 3 is / · Oleic acid I Lu and Shi Xi acid town, temple powder, gelatin, tragacanth, methyl, cut, quasi-methyl, methine Cellulose sodium and polyethylene σ ratio ketamine, ♦ Guangzhanzhai: agar, alginic acid and its sodium salt, foaming mixture. The applicable dosage will vary depending on the sex, age and weight of the patient, the route of administration, the nature of the condition and any associated treatment and will vary from 1 mg to 50 mg agomelatine every 24 hours. The daily dose of agomelatine should preferably be 25 mg daily and may increase to 50 mg per day. [Embodiment] Pharmaceutical Composition: A formulation of 1000 tablets each containing 25 mg of the active ingredient was prepared. 119756.doc 200808295 ----25 g — _62 g ......1.3 g ......9 g -------0.3 g ......30 g ------2.6 g N-[2 -(7-methoxynaphthyl)ethyl]acetamidactose monohydrate.......................... Stearic acid money ------------------------- Polyvinylpyridinone (P〇vidone)............., anhydrous Colloidal silica dioxide 夕-................... Sodium hydroxyacetate........................................................ .......................... Clinical study: The clinical study of relative placebo was performed on 21 patients. These 121 patients were randomized into two parallel groups and received either each (f) or cogmelatin or placebo. After two weeks of treatment and in the case of low response, the dose was increased to 50 mg per day in a double-blind study of patients receiving agomelatine using the IVRS system (interactive, acoustic response system). The treatment was carried out for 12 weeks. The efficacy is recommended by a health agency such as the Hamilton Anxiety Scale (Hamilt〇n M.? J. Neurol. • Neimmi3: g· Psyehiat·, 1959, 23, 56-62) or Evaluation of the evaluation tool of the Sheehan Disability Scale (International Clinical Psychopharmacology, 1996, 11, 8, 95). Also. Assess the acceptability profile. • The results obtained from the total score on the Hamilton scale (first evaluation criteria) show the 3.38 (p = 0·) between the group treated with agomelatine and the placebo group. Difference 040), which corresponds to clinically and statistically significant differences. The study also showed a good acceptability profile for the patient and there was no discontinuation syndrome when the treatment was discontinued. 119756.doc -10-

Claims (1)

200808295 X. Patent application scope: 1 · An Agmela>, agomelatine or 7^[2-(7-methoxy-;;__Caiqi)ethyl]acetamide and its hydrate The use of crystalline forms and addition salts with pharmaceutically acceptable acids or bases for the preparation of a medicament for the treatment of Generalized Anxiety Disorder. 2. The use of the requester, characterized in that the agomelatine is obtained in a formula. /3·: a pharmaceutical composition comprising Agomeira (iv) a hydrate, a crucible form and an addition salt to a pharmaceutically acceptable acid or base: A variety of pharmaceutically acceptable drugs for the treatment of generalized anxiety disorder, λ &&& 4. The pharmaceutical composition of claim 3, obtained in the form of crystal 11 "》戈吴拉汀系结结结 119756.doc 200808295 VII. Designation of representative drawings: (1) The representative representative of the case is: (none) (2) The symbol of the symbol of the representative figure is simple: Φ 8. If there is a chemical formula in this case, please reveal the characteristics that can best show the invention. Chemical formula: NHCOMe (I) 119756.doc